1. Field of the Invention
The present invention relates to a mass spectrometer for analyzing a sample gas separated by gas chromatography and to a method of analysis using the same.
2. Description of the Related Art
In the following description, gas chromatography will be abbreviated as GC, liquid chromatography will be abbreviated as LC, a mass spectrometer will be abbreviated as MS, an apparatus in which gas chromatography and a mass spectrometer are combined will be abbreviated as GC/MS (gas chromatography/mass spectrometer), atmospheric pressure chemical ionization will be abbreviated as APCI, chemical ionization will be abbreviated as CI, electron impact ionization will be abbreviated as El, and electro-spray ionization will be abbreviated as ESI.
Many studies for an attempt to use a mass spectrometer for diagnoses of diseases are in progress in recent years. In particular, a mass spectrometer is frequently used in order to search for a disease marker.
In a search for a disease marker, specimens are acquired respectively from a healthy person and from a patient of a specific disease, and then metabolites and proteins contained in the specimens are comprehensively analyzed with a mass spectrometer to find out a substance that differentiates between the healthy person and the patient. Gas samples such as breath or urine headspace gas, liquid samples such as blood, urine, saliva or tear, cells, and tissues are used as the specimens for searching for the disease marker. Numerous specimens must be measured in order to ensure reliability of the disease marker. Moreover, it is necessary to discover a small number of substances that differentiate between the healthy person and the patient among an extremely large number of substances contained in these specimens. Further, it is essential to identify the substance discovered as the disease marker so as to consider a relation between the disease marker and a mechanism of the development of the disease. In order to perform this operation efficiently, it is effective to use a combination of GC/APCI/MS and GC/EI/MS in the case of a gas sample or a combination of LC/APCI (or ESI)/MS and LC/EI/MS in the case of a liquid sample.
The APCI/MS is an apparatus for ionizing micro-amount of ingredients in a mixed sample by using ion-molecular reaction, and for thus detecting the ionized ingredients with high sensitivity, and is used for the analysis of micro-ingredients in environmental samples or biological samples. The APCI is a soft ionization method with which molecules hardly break down at the time of ionization. Accordingly, it is possible to measure a molecular weight of the molecules and also to measure individual molecular weights even when multiple substances enter an ion source to be ionized at the same time. Since several thousand types of substances are contained in the specimen, it is practically necessary to conduct separation of substances by the GC prior to ionization. However, as it is possible to detect multiple substances at the same time, it is only necessary to conduct rough separation for a short time period. For this reason, the APCI/MS is effective for measuring and comparing numerous specimens and for discovering different substances therein. Japanese Patent Application Publication No. Hei 9-15207 discloses an analyzer with high sensitivity in which GC and APCI/MS are combined for conducting analysis of various kinds of micro-impurities including special gases for use in semiconductor manufacturing. In the apparatus, a sample gas separated in the GC column is introduced in admixture with a carrier gas through a line to an APCI source and analyzed.
Meanwhile, the EI/MS is a mass spectrometer using a high energy ionization method in which a thermoelectron is caused to collide with a molecule. The EI/MS is capable of identifying a substance from a pattern of fragment ions generated by a breakup of a molecule at the time of ionization. As an example of combining the APCI/MS with the EI/MS, Non-patent Document 1 discloses the following method. In this method, substances are distributed at a tee after separation by GC, and then introduced to the APCI/MS and to the EI/MS, so that measurement is performed in the two MS at the same time.
Meanwhile, as an example of installing two types of ion sources onto one MS, Japanese Patent Application Publication No. Hei 11-307041 discloses an apparatus in which a first ionization chamber for CI, a second ionization chamber for EI, and a mass spectrometer part are serially in adjacent to with each other, and a passage port for passing ions is disposed between each of the ion sources. The sample gas enters the first ionization chamber and is introduced into the second ionization chamber through the passage port. The sample gas is ionized in a state of stopping an EI operation at the time of a CI operation while the sample gas is ionized in a state of stopping the CI operation at the time of the EI operation, thereby analyzing the introduced sample while switching the two ion sources.
Japanese Patent Application Publication No. 2000-357488 discloses an apparatus of separating ingredients flown out of a single LC by use of branch tee and to send the ingredients to two ion sources for the ESI and the APCI. It is possible to perform analyses in accordance with two ionization methods by switching the ion sources.
Meanwhile, as a method of separating a mixed sample at high degree, Patent Document 4 discloses an apparatus using two LC that apply different separation methods. A sample separated by the first LC is measured with a UV-visible spectrometer and absorbed separately by multiple trap columns, and is further separated by the second LC and measured with a mass spectrometer. In this way, the degree of separation of the sample containing various substances is improved.
[Patent Document 1] Japanese Patent Application Publication No. Hei 9-15207
[Patent Document 2] Japanese Patent Application Publication No. Hei 11-307041
[Patent Document 3] Japanese Patent Application Publication No. 2000-357488
[Patent Document 4] Japanese Patent Application Publication No. 2003-254955
[Non-patent Document 5] Journal of Agricultural and Food Chemistry (2002) p. 5400-5405